Trichostatin A increases radiosensitization of tongue squamous cell carcinoma via miR-375

Abstract

Trichostatin A (TSA), a histone deacetylase inhibitor, is used as an anti-carcinogenic and radiosensitizing agent in various cancers. However, the role and mechanism underlying its radiosensitization of tongue squamous cell carcinoma (TSCC) remains unclear. Thus, in this study we aimed to confirm the promotion of miR-375 expression by TSA, and to investigate the effects of TSA and miR-375 in the radiosensitivity of TSCC cells. The results showed that TSA had significant radiosensitizing effects on TSCC cells and miR-375 overexpression had effects similar to TSA in sensitizing these cells to radiotherapy. By contrast, miR-375 knockdown attenuated apoptosis induced by radiation combined with TSA. Mechanistically, the histone acetylation status of the miR-375 promoter region was increased by TSA, resulting in the upregulation of miR-375, which led to a decline of PDK1 and phosphorylated AKT. Taken together, our data suggest that TSA increases the radiosensitization and apoptosis in TSCC cells at least partially via miR-375, and TSA or miR-375 in combination with radiotherapy may provide a valuable approach for the treatment of TSCC.